Effect of cold-stress and indomethacin on the biosynthesis of gastric sulfated mucin in rats.
The biosynthesis of sulfated mucin in gastric tissue was investigated in cold-stress and indomethacin (CSI)-induced gastric ulcer models. To examine the synthesis of gastric sulfated mucin, [35S]H2SO4 (sulfate) incorporation into gastric mucin was measured. The treatment of CSI inhibited the incorporation of [35S]sulfate after 2 hr. The gastric acid hypersecretion or the formation of severe ulcer was observed at 1 or 4 hr after the CSI-treatment, respectively. Pibutidine hydrochloride (IT-066), a novel H2-receptor antagonist, (0.3 mg/kg, s.c.) inhibited the formation of ulcer and reversed the inhibition of mucin sulfation by the CSI-treatment, whereas atropine sulfate, a muscarinic receptor antagonist, (1.0 mg/kg, s.c.) did not inhibit the development of ulcer nor decrease in the mucin sulfation at 6 hr after the CSI-treatment. IT-066 inhibited the total acid output (T.A.O.) due to the reduction of the acidity in the gastric juice, whereas atropine inhibited the T.A.O. due to that of the volume. These results indicated that a different mode of action between IT-066 and atropine on gastric acid secretion influences their actions in the incorporation of [35S]sulfate and the formation of ulcer in the CSI-treated rat. Therefore, it is considered that the reduction of biosynthesis of gastric sulfated mucin following acid hypersecretion may be responsible for the formation of gastric ulcer.
Kiuchi
Y
Y
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Isobe
Y
Y
Kijima
H
H
Muramatsu
M
M
Higuchi
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D003080:Cold Temperature / Q000009:adverse effects*; D000431:Ethanol; D005752:Gastric Mucins / Q000096:biosynthesis*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D013312:Stress, Physiological / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005752:Gastric Mucins; D006635:Histamine H2 Antagonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D011725:Pyridines; D013431:Sulfates; C063924:IT 066; D000431:Ethanol; D001285:Atropine; D007213:Indomethacin